The prevalence of type 2 diabetes (T2D) has increased worldwide and doubled over the last two decades. It features among the top 10 causes of mortality and morbidity in the world. Cardiovascular ...disease is the leading cause of complications in diabetes and within this, heart failure has been shown to be the leading cause of emergency admissions in the United Kingdom. There are many hypotheses and well-evidenced mechanisms by which diabetic cardiomyopathy as an entity develops. This review aims to give an overview of these mechanisms, with particular emphasis on metabolic inflexibility. T2D is associated with inefficient substrate utilisation, an inability to increase glucose metabolism and dependence on fatty acid oxidation within the diabetic heart resulting in mitochondrial uncoupling, glucotoxicity, lipotoxicity and initially subclinical cardiac dysfunction and finally in overt heart failure. The review also gives a concise update on developments within clinical imaging, specifically cardiac magnetic resonance studies to characterise and phenotype early cardiac dysfunction in T2D. A better understanding of the pathophysiology involved provides a platform for targeted therapy in diabetes to prevent the development of early heart failure with preserved ejection fraction.
Background
Guidelines for hypertension vary in their preference for initial combination therapy or initial monotherapy, stratified by patient profile; therefore, we compared the efficacy and ...tolerability of these approaches.
Methods and Results
We performed a 1‐year, double‐blind, randomized controlled trial in 605 untreated patients aged 18 to 79 years with systolic blood pressure (BP) ≥150 mm Hg or diastolic BP ≥95 mm Hg. In phase 1 (weeks 0–16), patients were randomly assigned to initial monotherapy (losartan 50–100 mg or hydrochlorothiazide 12.5–25 mg crossing over at 8 weeks), or initial combination (losartan 50–100 mg plus hydrochlorothiazide 12.5–25 mg). In phase 2 (weeks 17–32), all patients received losartan 100 mg and hydrochlorothiazide 12.5 to 25 mg. In phase 3 (weeks 33–52), amlodipine with or without doxazosin could be added to achieve target BP. Hierarchical primary outcomes were the difference from baseline in home systolic BP, averaged over phases 1 and 2 and, if significant, at 32 weeks. Secondary outcomes included adverse events, and difference in home systolic BP responses between tertiles of plasma renin. Home systolic BP after initial monotherapy fell 4.9 mm Hg (range: 3.7–6.0 mm Hg) less over 32 weeks (P<0.001) than after initial combination but caught up at 32 weeks (difference 1.2 mm Hg range: −0.4 to 2.8 mm Hg, P=0.13). In phase 1, home systolic BP response to each monotherapy differed substantially between renin tertiles, whereas response to combination therapy was uniform and at least 5 mm Hg more than to monotherapy. There were no differences in withdrawals due to adverse events.
Conclusions
Initial combination therapy can be recommended for patients with BP >150/95 mm Hg.
Clinical Trial Registration
URL: http://www.ClinicalTrials.gov. Unique identifier: NCT00994617.
Abstract Objective The response of the RV following treatment of aortic stenosis is poorly defined, reflecting the challenge of accurate RV assessment. Cardiovascular magnetic resonance (CMR) is the ...established reference for imaging of RV volumes, mass and function. We sought to define the impact of transcatheter aortic valve implantation (TAVI) and surgical aortic valve replacement (SAVR) upon RV function in patients treated for severe aortic stenosis using CMR. Methods A 1.5T CMR scan was performed preoperatively and 6 months postoperatively in 112 (56 TAVI, 56 SAVR; 76 ± 8 years) high-risk severe symptomatic aortic stenosis patients across two UK cardiothoracic centres. Results TAVI patients were older (80.4 ± 6.7 vs. 72.8 ± 7.2 years, p < 0.05) with a higher STS score (2.13 ± 0.73 vs. 5.54 ± 3.41%, p < 0.001). At 6 months, SAVR was associated with a significant increase in RV end systolic volume (33 ± 10 vs. 37 ± 10 ml/m2 , p = 0.008), and decrease in RV ejection fraction (58 ± 8 vs. 53 ± 8%, p = 0.005) and tricuspid annular plane systolic excursion (22 ± 5 vs. 14 ± 3 mm, p < 0.001). Only 4 (7%) SAVR patients had new RV late gadolinium hyper-enhancement with no new cases seen in the TAVI patients at 6 months. Longer surgical cross-clamp time was the only predictor of increased RV end systolic volume at 6 months. Post-TAVI, there was no observed change in RV volumes or function. Over a maximum 6.3 year follow-up, 18(32%) of TAVI patients and 1(1.7%) of SAVR patients had died (p = 0.001). On multivariable Cox analysis, the RV mass at 6 m post-TAVI was independently associated with all-cause mortality (HR 1.359, 95% CI 1.108–1.666, p = 0.003). Conclusions SAVR results in a deterioration in RV systolic volumes and function associated with longer cross-clamp times and is not fully explained by suboptimal RV protection during cardiopulmonary bypass. TAVI had no adverse impact upon RV volumes or function.
Late, repetitive or chronic remote ischaemic conditioning (CRIC) is a potential cardioprotective strategy against adverse remodelling following ST-segment elevation myocardial infarction (STEMI). In ...the randomised Daily Remote Ischaemic Conditioning Following Acute Myocardial Infarction (DREAM) trial, CRIC following primary percutaneous coronary intervention (P-PCI) did not improve global left ventricular (LV) systolic function. A post-hoc analysis was performed to determine whether CRIC improved regional strain. All 73 patients completing the original trial were studied (38 receiving 4 weeks’ daily CRIC, 35 controls receiving sham conditioning). Patients underwent cardiovascular magnetic resonance at baseline (5–7 days post-STEMI) and after 4 months, with assessment of LV systolic function, infarct size and strain (longitudinal/circumferential, in infarct-related and remote territories). At both timepoints, there were no significant between-group differences in global indices (LV ejection fraction, infarct size, longitudinal/circumferential strain). However, regional analysis revealed a significant improvement in longitudinal strain in the infarcted segments of the CRIC group (from − 16.2 ± 5.2 at baseline to − 18.7 ± 6.3 at follow up, p = 0.0006) but not in corresponding segments of the control group (from − 15.5 ± 4.0 to − 15.2 ± 4.7, p = 0.81; for change: − 2.5 ± 3.6 versus + 0.3 ± 5.6, respectively,
p
= 0.027). In remote territories, there was a lower increment in subendocardial circumferential strain in the CRIC group than in controls (− 1.2 ± 4.4 versus − 2.5 ± 4.0,
p
= 0.038). In summary, CRIC following P-PCI for STEMI is associated with improved longitudinal strain in infarct-related segments, and an attenuated increase in circumferential strain in remote segments. Further work is needed to establish whether these changes may translate into a reduced incidence of adverse remodelling and clinical events. Clinical Trial Registration:
http://clinicaltrials.gov/show/NCT01664611
.
Aortic stiffness is increasingly used as an independent predictor of adverse cardiovascular outcomes. We sought to compare the impact of transcatheter aortic valve implantation (TAVI) and surgical ...aortic valve replacement (SAVR) upon aortic vascular function using cardiovascular magnetic resonance (CMR) measurements of aortic distensibility and pulse wave velocity (PWV).
A 1.5 T CMR scan was performed pre-operatively and at 6 m post-intervention in 72 patients (32 TAVI, 40 SAVR; age 76 ± 8 years) with high-risk symptomatic severe aortic stenosis. Distensibility of the ascending and descending thoracic aorta and aortic pulse wave velocity were determined at both time points. TAVI and SAVR patients were comparable for gender, blood pressure and left ventricular ejection fraction. The TAVI group were older (81 ± 6.3 vs. 72.8 ± 7.0 years, p < 0.05) with a higher EuroSCORE II (5.7 ± 5.6 vs. 1.5 ± 1.0 %, p < 0.05). At 6 m, SAVR was associated with a significant decrease in distensibility of the ascending aorta (1.95 ± 1.15 vs. 1.57 ± 0.68 × 10(-3)mmHg(-1), p = 0.044) and of the descending thoracic aorta (3.05 ± 1.12 vs. 2.66 ± 1.00 × 10(-3)mmHg(-1), p = 0.018), with a significant increase in PWV (6.38 ± 4.47 vs. 11.01 ± 5.75 ms(-1), p = 0.001). Following TAVI, there was no change in distensibility of the ascending aorta (1.96 ± 1.51 vs. 1.72 ± 0.78 × 10(-3)mmHg(-1), p = 0.380), descending thoracic aorta (2.69 ± 1.79 vs. 2.21 ± 0.79 × 10(-3)mmHg(-1), p = 0.181) nor in PWV (8.69 ± 6.76 vs. 10.23 ± 7.88 ms(-1), p = 0.301) at 6 m.
Treatment of symptomatic severe aortic stenosis by SAVR but not TAVI was associated with an increase in aortic stiffness at 6 months. Future work should focus on the prognostic implication of these findings to determine whether improved patient selection and outcomes can be achieved.
AIM: To conduct a systematic review relating myocardial strain assessed by different imaging modalities for prognostication following ST-elevation myocardial infarction(STEMI).METHODS: An online ...literature search was performed in Pub Med and OVID? electronic databases to identify any studies that assessed global myocardial strain parameters using speckle-tracking echocardiography(STE) and/or cardiac magnetic resonance imaging(CMR) techniques either myocardial tagging or feature tracking(FT) software in an acute STEMI cohort(days 0-14 post-event) to predict prognosis either development of major adverse cardiac events(MACE) or adverse left ventricular(LV) remodelling at follow-up(≥ 6 mo for MACE,≥ 3 mo for remodelling). Search was restricted to studies within the last 20 years. All studies that matched the pre-defined search criteria were reviewed and their results interpreted. Due to considerable heterogeneity between studies,metaanalysis was not performed.RESULTS: A total of seven studies(n = 7) were identified that matched the search criteria. All studies used STE to evaluate strain parameters- five(n = 5) assessed global longitudinal strain(GLS)(n = 5),one assessed GLS rate(GLS-R)(n = 1) and one assessed both(n = 1). Three studies showed that GLS independently predicted the development of adverse LV remodelling by multivariate analysis- odds ratio between 1.19(CI: 1.04-1.37,P < 0.05) and 10(CI: 6.7-14,P < 0.001) depending on the study. Four studies showed that GLS predicted the development of MACE- hazard ratio(HR) between 1.1(CI: 1-1.1,P = 0.006) and 2.34(1.10-4.97,P < 0.05). One paper found that GLS-R could significantly predict MACEHR 18(10-35,P < 0.001)- whilst another showed it did not. GLS <-10.85% had sensitivity/specificity of 89.7%/91% respectively for predicting the development of remodelling whilst GLS <-13% could predict the development of MACE with sensitivity/specificity of 100%/89% respectively. No suitable studies were identified that assessed global strain by CMR tagging or FT techniques.CONCLUSION: GLS measured acutely post-STEMI by STE is a predictor of poor prognosis. Further research is needed to show that this is true for CMR-based techniques.
ObjectiveTo compare the incidence of silent cerebral infarction and impact on cognitive function following transcatheter aortic valve implantation (TAVI) with the first-generation CoreValve ...(Medtronic, Minneapolis, Minnesota, USA) and second-generation Lotus valve (Boston Scientific, Natick Massachusetts, USA).DesignA prospective observational study comprising a 1.5 T cerebral MRI scan, performed preoperatively and immediately following TAVI, and neurocognitive assessments performed at baseline, 30 days and 1 year follow-up.SettingUniversity hospitals of Leeds and Leicester, UK.Patients66 (80.6±8.0 years, 47% male) patients with high-risk severe symptomatic aortic stenosis recruited between April 2012 and May 2015.Main outcome measuresIncidence of new cerebral microinfarction and objective decline in neurocognitive performance.ResultsAll underwent cerebral MRI at baseline and immediately following TAVI, and 49 (25 Lotus, 24 CoreValve) completed neurocognitive assessments at baseline, 30 days and 1 year. There was a significantly greater incidence of new cerebral microinfarction observed following the Lotus TAVI (23 (79%) vs 22 (59%), p=0.025) with a greater number of new infarcts per patient (median 3.5 (IQR 7.0) vs 2.0 (IQR 3.0), p=0.002). The mean volume of infarcted cerebral tissue per patient was equivalent following the two prostheses (p=0.166). More patients suffered new anterior (14 (48%) vs 2 (5%), p=0.001) and vertebrobasilar (15 (52%) vs 7 (19%), p=0.005) lesions following Lotus. Lotus was associated with a decline in verbal memory and psychomotor speed at 30 days. However, performance longitudinally at 1 year was preserved in all neurocognitive domains.ConclusionsThere was a higher incidence of silent cerebral microinfarction and a greater number of lesions per patient following Lotus compared with CoreValve. However, there was no objective decline in neurocognitive function discernible at 1 year following TAVI with either prosthesis.
To determine if global strain parameters measured by cardiovascular magnetic resonance (CMR) acutely following ST-segment Elevation Myocardial Infarction (STEMI) predict adverse left ventricular (LV) ...remodelling independent of infarct size (IS).
Sixty-five patients with acute STEMI (mean age 60 ± 11 years) underwent CMR at 1-3 days post-reperfusion (baseline) and at 4 months. Global peak systolic circumferential strain (GCS), measured by tagging and Feature Tracking (FT), and global peak systolic longitudinal strain (GLS), measured by FT, were calculated at baseline, along with IS. On follow up scans, volumetric analysis was performed to determine the development of adverse remodelling - a composite score based on development of either end-diastolic volume index EDVI ≥20% or end-systolic volume index ESVI ≥15% at follow-up compared to baseline.
The magnitude of GCS was higher when measured using FT (-21.1 ± 6.3%) than with tagging (-12.1 ± 4.3; p < 0.001 for difference). There was good correlation of strain with baseline LVEF (r 0.64-to 0.71) and IS (ρ -0.62 to-0.72). Baseline strain parameters were unable to predict development of adverse LV remodelling. Only baseline IS predicted adverse remodelling - Odds Ratio 1.05 (95% CI 1.01-1.10, p = 0.03), area under the ROC curve 0.70 (95% CI 0.52-0.87, p = 0.04).
Baseline global strain by CMR does not predict the development of adverse LV remodelling following STEMI.
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